Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Department of Anesthesiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710049, China; Shaanxi Provincial Center for Regenerative Medicine and Surgical Engineering, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
Bioelectrochemistry. 2024 Aug;158:108726. doi: 10.1016/j.bioelechem.2024.108726. Epub 2024 May 7.
Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.
气道中杯状细胞过度增殖和化生导致的黏液高分泌是慢性阻塞性肺疾病(COPD)的病理基础。临床试验已经证实了脉冲电场消融(PFA)治疗 COPD 的临床疗效,但其潜在机制尚不清楚。本研究建立了富含杯状细胞的 COPD 细胞和动物模型,以检测杯状细胞对 PFA 的敏感性。采用舒万方程计算细胞的跨膜电位和细胞膜的电穿孔面积。我们发现,与 BEAS-2B 细胞相比,杯状细胞对低强度 PFA(250 V/cm-500 V/cm)更敏感。这归因于杯状细胞的体积更大,在相同的电场强度下可以形成更强的跨膜电位。此外,更大尺寸细胞的跨膜电位可以在更多区域达到细胞膜电穿孔阈值。台盼蓝染色证实,杯状细胞的 IRE 率高于 BEAS-2B 细胞。动物实验也证实,COPD 的气道上皮对 PFA 更敏感。我们得出结论,低强度 PFA 可以选择性地杀死 COPD 气道上皮中的杯状细胞,最终达到治疗 COPD 的治疗效果。